Neurodegeneration results from various different causes including genetic mutation, mitochondrial dysfunction, and the inability to handle increasing levels of oxidative or nitrosative stress can also lead to the progression of neurodegeneration. Substantial evidence from many in vitro and in vivo studies suggests that there is a commonality of events for the progression of many neurodegenerative diseases of aging. Some of these neurodegenerative diseases include Parkinson's disease (PD), Huntington's disease, Amyotrophic Lateral Sclerosis (ALS), and among the most common of the neurodegenerative disorders is Alzheimer's disease (AD). Mounting evidence in AD as well as in most neurodegenerative diseases shows an association with oxidative and nitrosative stress. Nitrosative stress and cell damage result when reactive nitrogen species (RNS) act together with reactive oxygen species (ROS).
Reactive oxygen species and reactive nitrogen species are formed during normal metabolism but an imbalance may result from the increased production of free radicals or from the failure of antioxidants and antioxidant enzymes to adequately scavenge the damaging molecules. This imbalance has been documented to be involved in AD. Several studies provide clear evidence that RNS, in particular peroxynitrite formation, contributes to the pathologies of chronic neurodegenerative diseases such as Parkinson's disease, AD, multiple sclerosis, and ALS. Peroxynitrite is formed from the reaction of nitric oxide radical with superoxide. Mitochondrial injury is believed to be a primary cause of peroxynitrite-promoting neurotoxic effects. Widespread peroxynitrite-mediated damage is seen in brain tissue from AD in the form of increased protein nitration in neurons.
However, the administration of antioxidants and antioxidant enzymes to treat diseases due to increased ROS and RNS in human clinical trials heretofore have been less than satisfactory due to issues with bioavailability and stability after administration.
The scientific community has known since 1959 that tobacco use has apparent protective effects against Parkinson's disease, and some animal models suggest that this protective effect arises from nicotine itself. Nicotine, therefore, represents a candidate “lead” neuroprotective drug for those diagnosed with early-stage PD. However, tremendous biological, political and ideological hurdles still apply to both smoking and the use of nicotine patches for treatment of PD. One of the main reasons for the unsuccessful clinical effect of nicotine in PD stems from the low degree of its bioavailability. While smoking, where nicotine is readily available to blood and then to brain, has been a powerful protective factor in the onset and progression of PD, nicotine patches do not replicate the protective effect due to its slow approach to the brain.
Thus, there remains an unmet need for improved methods for the prevention and/or treatment of neurodegeneration, in particular, Parkinson's disease.